International Subarachnoid Aneurysm Trial - ISAT part II: study protocol for a randomized controlled trial.

BACKGROUND: The International Subarachnoid Aneurysm Trial (ISAT) demonstrated improved one-year clinical outcomes for patients with ruptured intracranial aneurysms treated with endovascular coiling compared to surgical clipping. Patients included in ISAT were mostly good grade subarachnoid hemorrhage (SAH) patients with small anterior circulation aneurysms. The purported superiority of coiling is commonly extrapolated to patients not studied in the original trial or to those treated using new devices not available at the time. Conversely, many patients are treated by clipping despite ISAT, because they are thought either to be better candidates for surgery, or to offer more durable protection from aneurysm recurrences. These practices have never been formally validated. Thus, for many ruptured aneurysm patients the question of which treatment modality leads to a superior clinical outcome remains unclear. METHODS/TRIAL DESIGN: ISAT II is a pragmatic, multicenter, randomized trial comparing clinical outcomes for non-ISAT patients with subarachnoid hemorrhage allocated to coiling or clipping. Inclusion criteria are broad. The primary end-point is the incidence of poor clinical outcome (defined as mRS >2) at one year, just as in ISAT. Secondary end-points include measures of treatment safety for a number of pre-specified subgroups, with efficacy end-points including the presence of a major recurrence at one year; 1,896 patients (862 each arm plus 10% losses) are required to demonstrate a significant difference between coiling and clipping, hypothesizing 23% and 30% poor clinical outcome rates, for coiling and clipping, respectively. The trial should involve at least 50 international centers, and will take approximately 12 years to complete. Analysis will be by intention-to-treat.